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CLINICAL STUDY: ENDOTHELIAL FUNCTION

Radiation therapy impairs endothelium-dependent vasodilation in humans

Joshua A. Beckman, MD, FACC^*, Avni Thakore, MS^*, Barbara H. Kalinowski, RN, MSN, Jay R. Harris, MD and Mark A. Creager, MD, FACC^*

^* Vascular Medicine Section, Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA
Department of Radiation Oncology, Brigham and Women’s Hospital, Boston, Massachusetts, USA

Manuscript received May 19, 2000; revised manuscript received October 6, 2000, accepted November 17, 2000.

Reprint requests and correspondence: Dr. Mark A. Creager, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115
mcreager{at}partners.org

OBJECTIVES

The objective of this study was to test the hypothesis that external-beam radiation induces a chronic impairment of endothelium-dependent vasodilation.

BACKGROUND

Radiation therapy is used commonly in the treatment of cancer and is associated with an increased incidence of adverse vascular events related to the field of radiation, including stroke and myocardial infarction. As endothelial injury is central to the pathogenesis of vascular diseases, we hypothesized that radiotherapy induces arterial endothelial dysfunction.

METHODS

Sixteen women with unilateral breast cancer who underwent standard external-beam radiation therapy to the breast and axilla >3 years before enrollment and ten healthy women were studied. Vascular ultrasonography was used to image both the artery exposed to radiation and the contralateral artery. Flow-mediated, endothelium-dependent vasodilation and endothelium-independent vasodilation to nitroglycerin of both axillary arteries were measured.

RESULTS

Endothelium-dependent vasodilation was significantly impaired in the irradiated axillary arteries compared with the contralateral, nonirradiated arteries (–0.4 ± 0.4% vs. 3.2 ± 0.8%, p < 0.001) and also compared with control subjects’ arteries (–0.4 ± 0.4% vs. 2.5 ± 0.6%, p < 0.001). In contrast, endothelium-independent vasodilation was greater in the arteries that received radiation compared with the contralateral arteries (3.8 ± 0.5% vs. 2.0 ± 0.4%, p < 0.05) and also compared with control arteries (3.8 ± 0.5% vs. 2.5 ± 0.4%, p < 0.05).

CONCLUSIONS

External beam radiation therapy impairs endothelium-dependent vasodilation of conduit arteries, implicating a decrease in the bioavailability of nitric oxide. These abnormalities may contribute to the development of arterial occlusive disease and associated clinical events.

Abbreviations and Acronyms   BP = blood pressure   LDL = low density lipoprotein   MI = myocardial infarction

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